I recommend this article to those here who are following a treatment developed by Dr. Robert Gatenby. This will give you the background on the development of his work and answer some questions you might have with regard to your own treatment.
Happy to discuss with anyone who reads it and I can provide a digital copy in WORD if you can't access it through the link.
wired.com/story/cancer-trea...
Dr. Write
As an engineer and believer in science and mathematical modeling, your sharing of this article has inspired me. Loved Gatenby's approach, hope it has success.
That article is indeed interesting, and in Australia the only good rabbit is a dead one, because they out-breed their enemies, foxes, wild dogs and cats, which like rabbits where all introduced to Oz from Europe and the effect was that many native animal species with negligible effect on growing crops were wiped out by the introduced carnivores. The rabbits chewed all the greenest shoots of planted crops, causing huge farming losses. Myxomatosis was a disease introduced to wipe out rabbits and it succeeded fairly well until the inevitable survivors began to breed so new biological agents that only affect rabbits have to be contrived and released to keep rabbit numbers down. It would be impossible to practice a start stop program with on bio agent so that when number declined, you stopped releasing it so resistance didn't increase with constant doses of bio agent.
BAT therapy with Pca tries to apply Gatenby's idea that after giving ADT, Pca is supressed, and testosterone receptors increase and the Pca manages to live on a vastly smaller amount of T in a castrated man. Then to give a big dose of T and this floods the Pca cells and the overload of T is toxic, so many Pca cells die, and then this is repeated and the Pca is finally killed this way, not just put to sleep for awhile. Nice idea, but not many are trying this 'cos it seems too risky. And men with bone mets just suffer huge pain with sudden megadose of T. Well, always there are survivors, and those will be found to make their own T defy anything the doctors do with T levels.
The Pca cells give small response to Cosadex, Zytiga, and anything else that interferes with their life, so the treatment modifies the disease, and remarkably, most still make Psa so a man knows Pca is alive, but he has no idea that its mutated and some cells have died, and been replaced with anti doctor DNA. Anti chemo as well, and anti anything else.
I'm having Lu177 therapy and taking enzalutamide as well. The enzal is supposed to make my Pca cells express more PsMa to attract more Lu177 to gather near the Pca cells, and inside them, in the small blood vessels the cancer nurtures to allow itself to grow, so maybe many types of Pca cells are now present in my many mets, the ones in bones are the hardest to kill, but anyway, I guess there will be survivors after each Lu177 infusion because Psa has not gone to 0.0 quickly. But it has gone from 25 to 5, not a bad result, but maybe the intermittent use of Lu177 every 8 weeks is better than having say a shot every 3 weeks, so that as Lu177 gathered at Pca cells lose radioactivity its replaced by a new dose with high radioactivity. But that is too simplistic, because maybe the spent Lu177 hangs around the tumour for a long time before they are moved away by blood stream and peed out via kidneys.
So one does not know if Lu177 wipes out many Pca cells but creates survivor cells resistant to beta particles which would then dominate the met sites, and these would mutate to not express PsMa and not be seen in PsMa Ga 68 scans and not be treatable, so the next dose of Lu177 is attracted by those cells that have not mutated only. But since the initial Pca and mutants are at the same site, maybe Lu177 just kills all it can, and it remains to be seen if the mutants that use more food energy choke out the other originals in low numbers thus leaving mostly mutants, and untreatable by anything known.
Nobody has suggested I have biopsy samples taken from Pca mets in my bones while treatment continues and have those samples analyzed. How does one take a bone met biopsy? drill a hole and poke in a needle, aahhh, the idea terrifies me, and might spread the mets. The cost of this is eye watering and maybe not predict anything that could be a benefit, so I am left to think that the spacing apart of my Lu177 is optimal, to get a worthwhile lengthening of life for most men getting treated. One could twiddle about altering dose levels and analyze and alter timing of the doses, but it seems that is too difficult to achieve and get a better outcome for more men for a longer time.
Now in Oz they are doing trials with Lu177 on men also taking ketruda and in my case I'm taking enzalutamide, a leading research doc said I should, she has done huge cellular research work and I hope she's right. Lu177 began to be used on men after everything else has failed, a last throw of the dice, but now a trial here is to be done on men at stage 1, without any mets, and it seems quite promising, because there might be survivors, sure, they'll be resistant to beta particles, but may become more vulnerable to ADT and chemo.
The trend in Germany is for men to have Lu177 as early as possible, because its so much harder to reduce big fat mets than small mets, especially when they are in bones which are beginning to be weakened and break, causing terrible pain and eventually a man begs for Nembutal.
I've been off my bicycle for about 9 weeks, Pca progress in bones seems to have been seriously slowed by 3 shots of Lu177, and biggest mets were about pea sized, and I've seen them in my scans. Among the many, there is one above right hip joint in pelvis, one below joint in femur, and local 20Grey was given during last month to assist the action of Lu177, which often does not work much on bone mets until after at least 2 infusions. Anyway, the soreness in my hip has reduced, and yesterday I cycled 15km and today about 21km and so I feel a lot better.
There is no possible way I could change the way I am being given this nuclide systemic targeted radiation, I must take it or leave it, and I could not ever think the greatest Pca experts have not been giving large thought to how mutant cells become dominant in a met site; I have read that Gatenby's ideas have been much considered, but maybe not because cancer mutations are like adaptive mutations in moths that eat cabbages despite heavy use of pesticides. There IS a similarity in thinking, but cancer is a little different to a whole living animal. If I were to become able to resist effects of an atomic war, I might try mutating to be like a cockroach; they can do remarkably well in places and conditions we now would hate.
Thanks for the link.
We are a long way off getting a cure for all Pca, and many other cancers, and methinks that maybe the best hope is to be able to alter our immune cells to recognise cancer as a rogue cell, and the altered immune cells go on to replicate with this ability, so once you have a treatment, you get your own body's resources to work against cancer like it does against a huge variety of stuff that finds its way into our bodies, or is created by our bodies. Mankind is only beginning to see the complexities involved and I hope I survive long enough for an immune therapy to evolve that is simple, cheap and effective, and does more than Provenge, thus making chemo and other things seem primitive and a waste of time and money.
I hope all of you can access what is now only experimental but sometimes spectacularly successful.
Today was hugely nice day, good cycle to lunch, then coffee by a lake and I talked an hour to a cyclist I met, then smelt a live jazz band in the city, so I headed in close to listen awhile, ah, good jazz, well played, just guys and gals jamming, and a gem of an autumn musical experience, great afternoon sunshine, so happy to be alive.
My bicycle was happy too. It has married me, and on Sundays what do wives demand? "Listen here you man thing, youse jus' gotta ride me today, OK?"
Keep well if you can,
Patrick Turner.
what's this about "men with bone mets just suffer huge pain with sudden megadose of T". Does cessation of aberaterone cause this? I am of course on monthly Leuprorelin jabs anyway and these will continue
In information about BAT I read that to be suitable for the treatment you could not have bone mets because the high T dose causes the pain,
The abiraterone may have nothing to do with pain, but I suggest you read what Dr Sam Denmead at John Hopkins hospital says about BAT because he conducted a trial funded by US army for BAT. Mixed results on that, but you'll have to Google that.
Patrick Turner.
Hi Patrick, the Denmeade/Johns Hopkins trials all screened out patients with symptoms because of that fear that high T might increase existing pain. However the actual evidence that high T causes pain in bone mets is sparse and ambiguous. There are some cases where it did increase pain but there are other cases where it relieved existing pain, so who knows? The advantage with BAT is you can quickly go back to the castrate state if nasty side effects make themselves evident. The risks of BAT have often been grossly overstated because of the still current lazy fantasy that :"hi t is fuel for cancer". That is false, wrong, bullshit, never had any credible evidence.
Very pleased you are responding to Lu177 and feeling better.
Well Pca does seem to be a testosterone junky, afaik. I got 6 years of good suppression with only plain old ADT.
Over time, the Pca gets so pissed off by doctors starving it of T that is sets up drug labs within itself to make its own DHT that is worse that plain old T made in testicles. Then docs invented abiraterone to shut down these drug labs and an ally of testicles, the adrenal gland. Then Pca goes into Dark Method to grow and I ain't sure about the real bad nature it has by the time it laughs at the docs again. But chemo didn't do much. But its early days for Lu177, and I could bet my type of cancer will become like vicious rebels and hide in the hills and as soon as Aunty Lutetia stops shooting them up with beta particles, Pca rebels will come down from hills and hit back, so youse ain't seem nuttin yet, OK.
My instinct tells me my cancer is being made more untreatable by each treatment, and would it die if I fed it some overdoses of T as done in BAT?
Its like playing Russian Roulette, doing that one. Might have frightful pain and big boost to Psa; that'd be my luck.
Nice day here now,
Patrick Turner.
Patrick...for those men living here in the U.S. your knowledge about the clinical outcomes of LU177 is highly useful since many men consider the trip to Germany or Australia but if the treatment modality requires multiple and ongoing treatments that is a deal killer since it involves many trips by men who are not traveling well to the corner grocery store let alone overnight economy class to Oz. I think it is fair to say that many hoped Lu 177 to be a “ one and done “ treatment since it was thought the radioactive beta particle would attach to the PSMA protein sitting on top of the cancer cell and explode it into smithereens. If it is true that it it just damages the cell which then repairs, or certain cells are inherently radio resistant to the beta particle, then It may be just another remission agent, which being radioactive , may result in now unknown radioactive consequences the more it is given.
What you are pointing out to us is that the clinicians and researchers are trying to understand why the cancer cells live post treatment. Is the beta particle not damaging enough...thus the interest in the alpha particle of AC 225 ? Is the beta dose too low and increasing it wipes out things in addition to the salivary glands. Any papers you know of or may see in the future which deals with these questions would be worthy of a separate post. And thanks for this information
There is no known one shot nuclide therapy. Lu177, Ac225, Ra223 all require multiple doses, so if any of these things are not located near you then you'd have to move to where they are. I've only got to travel 300km by train to get my Lu177, and stay with my sister for 2 nights, and that's easy but 4 x 8 week treatment cycles is 8 months.
And it is not known yet why some men do not respond, or give little response, or have remission like response. I might get Psa to get down to say 1.0 after 4 shots, but then maybe 2 months later it has a doubling time of 2 months, so in 8 months I have Psa 32, back where I started, so the benefit would have been that I began at Psa 25, then at 16 months Psa is same as when I began, so the time gained alive is 16 months, but I cannot predict that accurately. Cost to stay alive would be $83 a day. But many men have Pca increase after all the known treatments have lowered their Psa for awhile. Its been my experience since diagnosis in 2009.
Patrick Turner.
If you are an American, how would you go about getting LU177 in Germany? My husband is still hormone sensitive so we're not eligible in the U.S. but his met burden is huge.
Rabbit foot for sale, three more available.....
Good Luck, Good Health and Good Humor.
j-o-h-n Monday 04/15/2019 6:42 PM DST (Uncle Sam's Birthday
Its no good being an anti rabbit extremist because the Easter Bunny has to Bring the eggs.
No good being anti Santa fanatic; the reindeers would be out of work, not to mention the toy makers.
Patrick Turner.
To P-T,
I just adore bunnies.... ya know the Playboy bunnies....
I'm pro Santa too, I just wish he would bring me a Playboy bunny....
Good Luck, Good Health and Good Humor.
j-o-h-n Monday 04/15/2019 10:32 PM DST (Uncle Sam's Birthday)
Oh how we all loved those Playboy Bunnies. The only trouble was none of us could have relied on them to stay with us for longer than a minute or three, and the expense of keeping their life expectations fully satisfied was far worse that having to hire Aunty Lutetia to shoot at our cancers with her quadruple barrel Beta particle gun, but someone said she looks Miss Superwoman, and boots, and the style, wow, and the smile...….
Maybe, a bone marrow transplant from cloned cells derived from Germaine Greer might be just the thing to cure any one of many men's ailments, Pca for sure, and I'll let you talk to your missus about what else could be used to prime up our dodgy immune system to make you better. Its extremely difficult to be better and as the ladies might want us to be considering that the older a man gets, the better he woz.
Has Unkel Sam done you some favours? No need to answer lest the letters pile up like an Alaskan snow drift.
Do I ride a bicycle tomorrow or not? I'll give it a try, just to answer that question.
Patrick Turner.
You had me at boots and a smile. We can at least enjoy the eye candy. Take care.
Every year on April 15, everyone in the U.S. contributes to Uncle Sam's bank account a/k/a TAXES.
Good Luck, Good Health and Good Humor.
j-o-h-n Tuesday 04/16/2019 4:43 PM DST
I read the article and have an appointment this Thursday with the MO mentioned in it who practices here in Oregon. She has several PCa patients being treated in this way and getting great results.
see my post Adaptive Therapy posted a few minutes ago. Please ask your MO if her patients and others are being documented so as to build up a large database that the NHS (for example) will recognise!
I would be very interested to hear what you learn at your next appointment. Thanks!
UPDATE: I met with the Oncologist (Board certified w/30 years practicing medicine) and we talked at length about adaptive therapy and how the trials are going at Moffett. Since their last published results, things have gone even better for the participants. The group of patients still haven't reached mean time to failure of ADT and are well beyond double the usual mean time of 16.5 months. She is not sure when they will publish more of the results publicly but they are very excited about how things have gone for the patients. I do align with the profile for going this route and will mimic the trial with her guidance. Now I'll be n of 1 in my own clinical trial.
Hello DrWrite, I have read the article and highly recommend it, along with the papers Gatenby and others have published. I gave a copy to my family doctor who loved it as well (as opposed to dense research papers, which he has an aversion to!). I have been following papers on evolutionary game theory for some time and recently decided to change my position from waiting for castration resistance (CR) to occur (i.e., passive mode) to proposing the commencement of abiraterone before CR at less than the maximum dose and regulating the dosage and timing according to my PSA with my MO. During the previous meeting 6 months ago he pooh-poohed the strategy and was quite negative (even upset, believe it or not). I am quite comfortable with following this path and will be more forceful with my MO next visit. Cheers, Phil
New slogan: ‘Our aim is to make you die of something else’.
Well maybe I still have time to be murdered by a jealous husband after all.
Good Luck, Good Health and Good Humor.
j-o-h-n Monday 04/15/2019 7:03 PM DST (Uncle Sam's Birthday)
from today’s NYT article
Excellent response to Ac-225-PSMA-617 in South Africa (update)
Access to research articles?
Nervous about this fenbendazole article
Modified Citrus pectin article
